Source 1primary paper2019
Toolkit/Light-Inducible Tuner
Light-Inducible Tuner
Also known as: LITer, LITer gene circuits
Taxonomy: Mechanism Branch / Architecture. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
Light-Inducible Tuner (LITer) is a mammalian optogenetic gene-circuit platform in which TetR is fused through the LOV2 light-sensitive domain to either a Tet-inhibitory peptide or a degradation tag. It enables light-controlled negative-feedback regulation of gene expression and was reported to reduce expression noise while providing tunable output control.
Usefulness & Problems
Why this is useful
LITer is useful for achieving more precise optogenetic control of transgene expression in mammalian or human cells, particularly when reduced cell-to-cell variability is important. The source literature states that these circuits should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology, and related biomedical contexts.
Problem solved
LITer was engineered to address the problem of noisy and insufficiently precise optogenetic gene regulation in mammalian cells. The reported solution is a light-responsive negative-feedback circuit architecture that improves control over expression magnitude while reducing gene expression noise relative to existing optogenetic systems.
Taxonomy & Function
Primary hierarchy
Mechanism Branch
Architecture: A composed arrangement of multiple parts that instantiates one or more mechanisms.
Mechanisms
DegradationDegradationlight-gated allosteric switchinglight-gated allosteric switchinglight-induced degradationlight-induced degradationnegative-feedback gene regulationnegative-feedback gene regulationTechniques
No technique tags yet.
Target processes
degradationInput: Light
Implementation Constraints
cofactor dependency: cofactor requirement unknownencoding mode: genetically encodedhost context: mammalian cellsimplementation constraint: context specific validationimplementation constraint: multi component delivery burdenimplementation constraint: spectral hardware requirementmammalian context: Truemodality: optogenetic negative-feedback gene circuitnegative feedback: Truenoise reduction: Trueoperating role: actuatoroptogenetic: Trueswitch architecture: multi component
The reported construct architecture uses TetR fused via the LOV2 light-sensitive domain to either a Tet-inhibitory peptide or a degradation tag. The evidence supports implementation as a multi-component optogenetic negative-feedback gene circuit in mammalian cells, but it does not provide practical details such as chromophore requirements, delivery modality, promoter design, or exact light wavelength.
The supplied evidence describes performance in mammalian or human cell gene circuits, but it does not provide broader validation across organisms, tissues, or in vivo settings. The available claims also do not specify illumination parameters, kinetic response characteristics, or comparative performance between the Tet-inhibitory-peptide and degradation-tag variants.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Source 2primary paper2019Nucleic Acids Research
Ranked Claims
The LITer gene circuit architecture was used to control expression of KRAS(G12V) and study downstream phospho-ERK levels and cellular proliferation.
Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation.
The LITer gene circuit architecture was used to control expression of KRAS(G12V) and study downstream phospho-ERK levels and cellular proliferation.
Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation.
The LITer gene circuit architecture was used to control expression of KRAS(G12V) and study downstream phospho-ERK levels and cellular proliferation.
Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation.
The LITer gene circuit architecture was used to control expression of KRAS(G12V) and study downstream phospho-ERK levels and cellular proliferation.
Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation.
The LITer gene circuit architecture was used to control expression of KRAS(G12V) and study downstream phospho-ERK levels and cellular proliferation.
Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation.
The LITer gene circuit architecture was used to control KRAS(G12V) expression and examine downstream phospho-ERK levels and cellular proliferation.
Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation.
The LITer gene circuit architecture was used to control KRAS(G12V) expression and examine downstream phospho-ERK levels and cellular proliferation.
Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation.
The LITer gene circuit architecture was used to control KRAS(G12V) expression and examine downstream phospho-ERK levels and cellular proliferation.
Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation.
The LITer gene circuit architecture was used to control KRAS(G12V) expression and examine downstream phospho-ERK levels and cellular proliferation.
Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation.
The LITer gene circuit architecture was used to control KRAS(G12V) expression and examine downstream phospho-ERK levels and cellular proliferation.
Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation.
The LITer toolset uses TetR fused with either a Tet-Inhibitory peptide or a degradation tag through the LOV2 light-sensitive domain.
We build a toolset of these noise-reducing Light-Inducible Tuner (LITer) gene circuits using the TetR repressor fused with a Tet-Inhibitory peptide (TIP) or a degradation tag through the light-sensitive LOV2 protein domain.
The LITer toolset uses TetR fused with either a Tet-Inhibitory peptide or a degradation tag through the LOV2 light-sensitive domain.
We build a toolset of these noise-reducing Light-Inducible Tuner (LITer) gene circuits using the TetR repressor fused with a Tet-Inhibitory peptide (TIP) or a degradation tag through the light-sensitive LOV2 protein domain.
The LITer toolset uses TetR fused with either a Tet-Inhibitory peptide or a degradation tag through the LOV2 light-sensitive domain.
We build a toolset of these noise-reducing Light-Inducible Tuner (LITer) gene circuits using the TetR repressor fused with a Tet-Inhibitory peptide (TIP) or a degradation tag through the light-sensitive LOV2 protein domain.
The LITer toolset uses TetR fused with either a Tet-Inhibitory peptide or a degradation tag through the LOV2 light-sensitive domain.
We build a toolset of these noise-reducing Light-Inducible Tuner (LITer) gene circuits using the TetR repressor fused with a Tet-Inhibitory peptide (TIP) or a degradation tag through the light-sensitive LOV2 protein domain.
The LITer toolset uses TetR fused with either a Tet-Inhibitory peptide or a degradation tag through the LOV2 light-sensitive domain.
We build a toolset of these noise-reducing Light-Inducible Tuner (LITer) gene circuits using the TetR repressor fused with a Tet-Inhibitory peptide (TIP) or a degradation tag through the light-sensitive LOV2 protein domain.
The authors engineered optogenetic negative-feedback gene circuits in mammalian cells for noise-reduced precise gene expression control.
Here, we engineer optogenetic negative-feedback gene circuits in mammalian cells to achieve noise-reduction for precise gene expression control.
The authors engineered optogenetic negative-feedback gene circuits in mammalian cells for noise-reduced precise gene expression control.
Here, we engineer optogenetic negative-feedback gene circuits in mammalian cells to achieve noise-reduction for precise gene expression control.
The authors engineered optogenetic negative-feedback gene circuits in mammalian cells for noise-reduced precise gene expression control.
Here, we engineer optogenetic negative-feedback gene circuits in mammalian cells to achieve noise-reduction for precise gene expression control.
The authors engineered optogenetic negative-feedback gene circuits in mammalian cells for noise-reduced precise gene expression control.
Here, we engineer optogenetic negative-feedback gene circuits in mammalian cells to achieve noise-reduction for precise gene expression control.
The authors engineered optogenetic negative-feedback gene circuits in mammalian cells for noise-reduced precise gene expression control.
Here, we engineer optogenetic negative-feedback gene circuits in mammalian cells to achieve noise-reduction for precise gene expression control.
LITer circuits provide nearly 4-fold gene expression control.
These LITers provide a range of nearly 4-fold gene expression control
gene expression control range 4 fold
LITer circuits provide nearly 4-fold gene expression control.
These LITers provide a range of nearly 4-fold gene expression control
gene expression control range 4 fold
LITer circuits provide nearly 4-fold gene expression control.
These LITers provide a range of nearly 4-fold gene expression control
gene expression control range 4 fold
LITer circuits provide nearly 4-fold gene expression control.
These LITers provide a range of nearly 4-fold gene expression control
gene expression control range 4 fold
LITer circuits provide nearly 4-fold gene expression control.
These LITers provide a range of nearly 4-fold gene expression control
gene expression control range 4 fold
LITer circuits provide nearly 4-fold gene expression control and up to five-fold noise reduction relative to existing optogenetic systems.
These LITers provide nearly a range of 4-fold gene expression control and up to five-fold noise reduction from existing optogenetic systems.
gene expression control range 4 foldnoise reduction versus existing optogenetic systems 5 fold
LITer circuits provide nearly 4-fold gene expression control and up to five-fold noise reduction relative to existing optogenetic systems.
These LITers provide nearly a range of 4-fold gene expression control and up to five-fold noise reduction from existing optogenetic systems.
gene expression control range 4 foldnoise reduction versus existing optogenetic systems 5 fold
LITer circuits provide nearly 4-fold gene expression control and up to five-fold noise reduction relative to existing optogenetic systems.
These LITers provide nearly a range of 4-fold gene expression control and up to five-fold noise reduction from existing optogenetic systems.
gene expression control range 4 foldnoise reduction versus existing optogenetic systems 5 fold
LITer circuits provide nearly 4-fold gene expression control and up to five-fold noise reduction relative to existing optogenetic systems.
These LITers provide nearly a range of 4-fold gene expression control and up to five-fold noise reduction from existing optogenetic systems.
gene expression control range 4 foldnoise reduction versus existing optogenetic systems 5 fold
LITer circuits provide nearly 4-fold gene expression control and up to five-fold noise reduction relative to existing optogenetic systems.
These LITers provide nearly a range of 4-fold gene expression control and up to five-fold noise reduction from existing optogenetic systems.
gene expression control range 4 foldnoise reduction versus existing optogenetic systems 5 fold
LITer circuits reduce gene expression noise by up to 5-fold relative to existing optogenetic systems.
and up to 5-fold noise reduction from existing optogenetic systems
noise reduction 5 fold
LITer circuits reduce gene expression noise by up to 5-fold relative to existing optogenetic systems.
and up to 5-fold noise reduction from existing optogenetic systems
noise reduction 5 fold
LITer circuits reduce gene expression noise by up to 5-fold relative to existing optogenetic systems.
and up to 5-fold noise reduction from existing optogenetic systems
noise reduction 5 fold
LITer circuits reduce gene expression noise by up to 5-fold relative to existing optogenetic systems.
and up to 5-fold noise reduction from existing optogenetic systems
noise reduction 5 fold
LITer circuits reduce gene expression noise by up to 5-fold relative to existing optogenetic systems.
and up to 5-fold noise reduction from existing optogenetic systems
noise reduction 5 fold
LITer gene circuits enable optogenetic negative-feedback control of gene expression in mammalian cells.
Here, we engineer optogenetic gene circuits into mammalian cells to achieve noise-reduction for precise gene expression control by genetic, in vitro negative feedback.
LITer gene circuits enable optogenetic negative-feedback control of gene expression in mammalian cells.
Here, we engineer optogenetic gene circuits into mammalian cells to achieve noise-reduction for precise gene expression control by genetic, in vitro negative feedback.
LITer gene circuits enable optogenetic negative-feedback control of gene expression in mammalian cells.
Here, we engineer optogenetic gene circuits into mammalian cells to achieve noise-reduction for precise gene expression control by genetic, in vitro negative feedback.
LITer gene circuits enable optogenetic negative-feedback control of gene expression in mammalian cells.
Here, we engineer optogenetic gene circuits into mammalian cells to achieve noise-reduction for precise gene expression control by genetic, in vitro negative feedback.
LITer gene circuits enable optogenetic negative-feedback control of gene expression in mammalian cells.
Here, we engineer optogenetic gene circuits into mammalian cells to achieve noise-reduction for precise gene expression control by genetic, in vitro negative feedback.
LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology, and other biomedical research fields.
Overall, these novel LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology, and other biomedical fields of research.
LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology, and other biomedical research fields.
Overall, these novel LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology, and other biomedical fields of research.
LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology, and other biomedical research fields.
Overall, these novel LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology, and other biomedical fields of research.
LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology, and other biomedical research fields.
Overall, these novel LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology, and other biomedical fields of research.
LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology, and other biomedical research fields.
Overall, these novel LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology, and other biomedical fields of research.
Approval Evidence
2 sources9 linked approval claimsfirst-pass slug light-inducible-tuner
We build a toolset of these noise-reducing Light-Inducible Tuner (LITer) gene circuits using the TetR repressor fused with a Tet-Inhibitory peptide (TIP) or a degradation tag through the light-sensitive LOV2 protein domain.
Source:
We build a toolset of these noise-reducing Light-Inducible Tuner (LITer) gene circuits using the TetR repressor fused with a Tet-inhibiting peptide (TIP) or a degradation tag through the light-sensitive LOV2 protein domain.
Source:
applicationsupports
The LITer gene circuit architecture was used to control expression of KRAS(G12V) and study downstream phospho-ERK levels and cellular proliferation.
Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation.
Source:
applicationsupports
The LITer gene circuit architecture was used to control KRAS(G12V) expression and examine downstream phospho-ERK levels and cellular proliferation.
Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation.
Source:
compositionsupports
The LITer toolset uses TetR fused with either a Tet-Inhibitory peptide or a degradation tag through the LOV2 light-sensitive domain.
We build a toolset of these noise-reducing Light-Inducible Tuner (LITer) gene circuits using the TetR repressor fused with a Tet-Inhibitory peptide (TIP) or a degradation tag through the light-sensitive LOV2 protein domain.
Source:
engineering outcomesupports
The authors engineered optogenetic negative-feedback gene circuits in mammalian cells for noise-reduced precise gene expression control.
Here, we engineer optogenetic negative-feedback gene circuits in mammalian cells to achieve noise-reduction for precise gene expression control.
Source:
performancesupports
LITer circuits provide nearly 4-fold gene expression control.
These LITers provide a range of nearly 4-fold gene expression control
Source:
performancesupports
LITer circuits provide nearly 4-fold gene expression control and up to five-fold noise reduction relative to existing optogenetic systems.
These LITers provide nearly a range of 4-fold gene expression control and up to five-fold noise reduction from existing optogenetic systems.
Source:
performancesupports
LITer circuits reduce gene expression noise by up to 5-fold relative to existing optogenetic systems.
and up to 5-fold noise reduction from existing optogenetic systems
Source:
tool capabilitysupports
LITer gene circuits enable optogenetic negative-feedback control of gene expression in mammalian cells.
Here, we engineer optogenetic gene circuits into mammalian cells to achieve noise-reduction for precise gene expression control by genetic, in vitro negative feedback.
Source:
use casesupports
LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology, and other biomedical research fields.
Overall, these novel LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology, and other biomedical fields of research.
Source:
Comparisons
Source-backed strengths
In the cited studies, LITer circuits provided nearly 4-fold gene expression control and up to 5-fold noise reduction relative to existing optogenetic systems. The platform was also applied to control KRAS(G12V) expression and assess downstream phospho-ERK levels and cellular proliferation, supporting utility in signaling-perturbation experiments.
Ranked Citations
- 1.
- 2.